This proposal involves a study of the pharmacological basis of coumarin anticoagulant action. These agents are used therapeutically to decrease the hepatic synthesis of the prothrombin complex in thromboembolic diseases, an action readily reversed by vitamim K. Our recent studies have demonstrated that the anticoagulants cause a decreased rate of incorporation of carbohydrate moieties into prothrombin and that this inhibitory action is reversed by vitamin K. We plan to investigate the mechanism of anticoagulant action using three principal approaches: 1. Establish any possible alterations in the carbohydrate sequences of prothrombin attributable to these agents. 2. Isolate and define the characteristics of the liver prothrombin precursor which occurs with anticoagulant treatment (and in vitamin K deficiency) and demonstrate its precursor-product relationship to circulating prothrombin. 3. Examine the effects of the anticoagulants on liver glycosyl transferase activities, especially with respect to their manganese cofactor function.